1. Field of the Invention
The invention relates to a device for manipulation of small volume droplets consisting of a few nanoliters to a few microliters. The displacement device uses electrostatic forces to displace small liquid volumes.
2. Description of the Background Art
Liquids are increasingly important in small components. Thus, labs-on-chips are used in many studies, mainly for biology, chemistry and optics. In some cases, micro-fluidics consists of making small volumes of liquid circulate in micro-machined ducts. For example, this means that a biological protocol can be applied on a very small sample volume. At the present time it is recognized that there are many advantages in minimizing analysis volumes, for example cost reductions, and improved speed and sensitivity.
However, miniaturizing the section of ducts also introduces a large number of difficulties. Firstly, it is difficult to control fluid displacements in these micro-ducts. Secondly, physicochemical interactions between liquids and the walls become predominant. Capillarity phenomena play an essential role, which requires very high quality surface conditions (roughness, physicochemistry). Similarly, phenomena for absorption of biological entities at the wall surface can limit reaction efficiencies. Thus, it is often necessary to apply specific surface treatments on the walls of ducts or to add different substances in biological protocols to limit these absorption phenomena. The article entitled “Miniaturized flow-through PCR with different template types in a silicon chip thermocycler” by Ivonne Schneegaβ et al., Lab on a Chip, 2001, 1, pages 42–49, contains an example.
Another difficulty with micro-fluidics in micro-ducts is connecting the component to the outside world. Connection of capillaries to a micro-component is one difficulty encountered in making labs on chips. Furthermore, inputs/outputs of the various liquids from or to external fluid storage systems have to be managed, while limiting dead volumes.
Another method of displacing small fluid volumes consists of manipulating an interface between two immiscible fluids. For example, document FR-A-2 548 431 divulges a device with electrical control of the displacement of a dielectric liquid. A liquid droplet is placed between two planes containing electrode pairs. The permittivity of the liquid droplet is greater at its environment defined by the space between the two planes comprising the electrodes. The displacement is controlled electrically by applying electric voltages to the electrode pairs. In this document, the displacement is explained by the existence of a dielectric force resulting from a difference in permittivity between the droplet and its environment and by electric field gradients resulting from applied voltages.
More precisely, the dielectric force tends to attract the fluid with a higher permittivity towards areas in which the field is more intense. This force is capable of overcoming surface tension forces, which explains displacement of the droplet.
Document FR-A-2 548 431 also recommends that the wettability of the liquid on the walls should be low. A silane (aminopropyltrimethoxysilyl chloride) type surface treatment is used to make the surfaces only very slightly wetting.
Therefore, this principle is applicable to isolating liquids, however a very slightly conducting liquid may also be used provided that an alternating voltage is used. The article “Mouvement d'un fluide en présence d'un champ électrique—Movement of a fluid in the presence of an electric field” by Pierre Atten, D 2850, Techniques de l'Ingénieur, Paris, describes the existence of electrostatic forces within fluids. In particular, it states that for two “perfectly insulating immiscible media and for an alternating voltage with a sufficiently high frequency f (f>>1/τ, where τ is the characteristic relaxation time of the space charge), only the permittivity skip at the interface contributes to the electric force”.
A configuration similar to the description in document FR-A-2 548 431 is described in the article “Electrowetting-based actuation of liquid droplets for microfluidic applications” by Michael G. Pollack et al., Applied Physics Letters, Vol. 77, No. 11, pages 1725 and 1726, Sep. 11, 2000. A water droplet is placed between two planes containing electrodes. The electrodes are covered with an electrically insulating layer that is made very hydrophobic by a thin deposit of Teflon®. The displacement principle is explained by electrocapillarity or electrowetting phenomena. The component presented in this article is capable of displacing 0.7 to 1 μl droplets with voltages of 120 V.
There are also methods of displacing conducting liquid droplets. For example, the article “Microactuation by continuous electrowetting phenomenon and silicon deep RIE process”, by Junghoon Lee et al., DSC-Vol. 66, Micro-Electro-Mechanical Systems (MEMS)-1998, ASME 1998 presents a method for displacing mercury droplets in a duct full of electrolyte by electrowetting.
Electrocapillarity has been studied for a long time (Lippman, 1875). A formulation is given in the article “Electrocapillarité et mouillage de films isolants par l'eau—Electrocapillarity and wetting of insulating films by water”, by Bruno Berge, C. R. Acad. Sci. Paris, t.317, series II, pages 157–153, 1993. A non-dielectric liquid droplet is deposited on a substrate comprising an electrode covered by an insulator. A second electrode is dipped into the droplet. The droplet spreads when an electric voltage is applied between the two electrodes. In this article, the wetting angle of the droplet on the surface θ is expressed as a function of the electrostatic voltage V applied between the two electrodes by the relation (1):
                              cos          ⁢                                          ⁢                      θ            ⁡                          (              V              )                                      =                              cos            ⁢                                                  ⁢                          θ              ⁡                              (                O                )                                              +                                    1              2                        ⁢                                          ɛ                r                                            e                ⁢                                                                  ⁢                γ                                      ⁢                          V              2                                                          (        1        )                            where ∈r is the dielectric coefficient of the insulating layer with thickness e, and γ is the liquid-gas surface tension.        
The article “Moving droplets on asymmetrically structured surfaces”, by O. Sandre et al., Physical Review E., Vol. 60, No. 3, September 1999, uses theory and experiment to demonstrate that initiating a vibration of a droplet placed between two substrates with an asymmetric structure can cause displacement of this droplet. An asymmetric structure is described like grooving in a saw tooth shape. The droplet is made to vibrate by the application of an electrostatic field oscillating between two electrodes placed on each of the two substrates in turn.
The disadvantage of the devices described above is that the droplets have to be confined between two planes or in a duct. This makes assembly and use of the component complex. Capillary connection problems arise that have already been identified for micro-fluidics in ducts, in which electrical connections also have to be taken into account. There are also risks of phenomena for absorption of biological entities on the two planes confining the droplets.
Another method of displacing droplets was presented in the article “Electrical Actuation of liquid droplets for micro-reactor applications” by Masao Washizu, IEEE Industry Applications Society, Annual meeting, New Orleans, La., Oct. 5–9, 1997, and more recently in “Droplet Manipulation on a Superhydrophobic Surface for Microchemical Analysis” article by Altti Torkkeli et al., Transducers' 01 Eurosensors XV.
In this case, the system is open. A droplet is deposited directly on a surface. The surface comprises several inter-digitized electrodes covered by an insulating layer. The surface is made very hydrophobic. Activation is based on the presence of electrostatic forces generated by electrodes placed under the droplet. By modifying the potential of electrodes, the distribution of Maxwell stresses on the surface of the droplet is modified, and M. Washizu has demonstrated that this electrostatic pressure can cause displacement of the droplet.
Unlike the previous examples, this method requires a large number of electrodes. Furthermore, an operation to structure the insulating layer is described in the article by M. Washizu to guide the droplet during its displacement.
The latter two articles are insistent about the hydrophobic nature of the surfaces, and particularly Torkelli et al use demineralized water as the liquid. This can be very limiting for some biological applications, in which the addition of reagents makes the liquids wetting.
In prior art described above, application of an electrostatic field obtained with a set of electrodes causes the displacement of a liquid droplet. Different interpretations were given depending on the configurations of electrodes or the electrical properties of liquids (insulating, or weakly or strongly conducting liquids). Thus, there was a question of the strength of the dielectric volume, electro-capillarity, electro-wetting or electrostatic pressure. All of these various phenomena will be referred to as “electrostatic forces” throughout the rest of this description, although this term is not strictly accurate.